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Samarasekera et al. reported four patients with non-
paraneoplastic acute limbic encephalitis (ALE), who had negative testing for voltage-gated potassium channel auto-antibodies. We wish to report a patient with a previously unreported association of ALE with
hemophagocytic syndrome (HPS) and discuss the possible pathophysiology.
A 9-year-old boy, the second child of healthy non-consanguin...
A 9-year-old boy, the second child of healthy non-consanguineous parents, was well until he showed fever (day 0 of illness). On day 3, he had leukopenia; white blood cells (WBC) count 1,400/micro l, and a mild
consciousness disturbance. On day 4, the leukopenia had worsened; WBC count 900/micro l, and thrombocytopenia appeared; platelet count 79,000/micro l. The blood chemistry showed some abnormalities; aminotransferase 75 IU/l, ferritin 1,320 ng/ml and soluble interleukin
(IL)-2 receptor 1,930 (reference range 124-466) U/ml. Polymerase chain reaction, for cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpes virus 6, 7 and varicella-zoster virus, using peripheral blood or cerebro-spinal fluid (CSF), were all negative. Bone marrow aspiration revealed hemophagocytosis but no malignancy. On day 6, he had a transient loss of consciousness, and he had convulsions afterwards. Then, brain computed tomography and magnetic resonance imaging (MRI) did not detect any abnormalities. Methylprednisolone pulse (30 mg/kg/day for 3 days) and gamma globulin (400 mg/kg/day for 3 days) therapies were started on that
day. To control seizures, midazolam and phenobarbital were administered. On day 11, awake EEG showed no occipital theta or alpha activity with high
voltage slow wave. On day 12, peripheral blood natural killer (NK) cell activity was 7 (reference range 18-40)%. Consciousness disturbance was slowly improving and midazolam and phenobarbital were gradually replaced
by carbamazepine. On day 17, brain MRI showed bilateral claustral lesions. Perforin expressions in cytotoxic T and NK cells were not reduced. On day 24, brain MRI showed the widened lesions, involving bilateral claustrum and hippocampi. On day 26, the hematology and blood
chemistry showed normal results, including ferritin. Cytokines, including IL-2, 4, 6, 10, interferon-gamma and tumor necrosis factor-alpha, were examined with serum and CSF, all resulted within normal limits. On day
30, soluble IL-2 receptor and NK cell activity were 674 U/ml and 44 %, respectively. On day 33, forward and backward digit span length were 4 and 2, respectively. On day 34, brain MRI showed that bilateral claustral
lesions were reduced. On day 44, Wechsler Intelligence Scale for Children Third Edition showed borderline mentality, verbal IQ=81, performance IQ=75 and full-Scale IQ=76. Follow up brain MRI on day 124, showed no lesions.
The examinations with auto-antibodies against the glutamate receptors (GluR) delta 2 and epsilon 2 were prompted, using CSF on day 26, serum on day 26 and 124. Their results were non-specific, anti-GluR epsilon 2 IgG
was weakly positive in CSF on day26 and anti-GluR epsilon 2 IgM was positive in serum on day 124.
Our case is compatible with HPS, except ALE. Although HPS often accompanies CNS involvement, ALE associated with HPS has not been reported. We hypothesize two possible pathological mechanisms, that seem to be polar opposites. One plausible explanation is immunological augmentation, which could result in an auto-antibody production. And the other is immunological compromise, which could result in viral infection. The increased soluble IL-2 receptor could result from T-cell activation, which seems to comprise the former possibility. On the other hand,
reduced NK cell activity seems to comprise the latter. The data from our patient are inconclusive. Further work is required to establish the immunological basis for ALE.
Samarasekera SR, Vincent A, Welch JL, Jackson M, Nichols P, Griffiths TD. The course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies. J Neurol Neurosurg Psychiatry (in print).
Imashuku S, Hyakuna N, Funabiki T, Ikuta K, Sako M, Iwai A, et al.Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis. Cancer 2002;94:3023~31.